Lymphoproliferative disorder early after cardiac transplantation.
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Adult↗
Biomedical subjects
J E Ferguson
Publications and source records attributed to J E Ferguson.
The effects of inositol trisphosphates and inositol tetrakisphosphate on Ca2+ release and Cl- current pattern in the Xenopus laevis oocyte.
We report that Ins(1,3,4,5)P4 releases calcium from intracellular stores of intact Xenopus laevis oocytes, as indicated by two different techniques, Ca2(+)-sensitive microelectrodes and a fura-2 imaging system. Ins(1,3,4,5)P4 releases only 20% as much Ca2+ as the same amount of Ins(1,4,5)P3. This effect is not due to the conversion of the injected Ins(1,3,4,5)P4 to Ins(1,4,5)P3, which is known to release Ca2+, because the amount of [3H]Ins(1,3,4,5)P4 that is converted to Ins(1,4,5)P3 is extremely small, as determined using HPLC. Examination of the different current patterns induced by Ins(1,4,5)P3 and Ins(1,3,4,5)P4, when injected into voltage-clamped oocytes, provided further evidence that the Ins(1,3,4,5)P4 was not being converted back to Ins(1,4,5)P3. We investigated the effects of four compounds, three inositol trisphosphates (Ins(1,4,5)P3, Ins(2,4,5)P3, and Ins(1,3,4)P3), and Ins(1,3,4,5)P4, on Cl- current conductance in order to examine (1) the possible role of Ins(1,3,4,5)P4 in cell activation and (2) the relationships between intracellular Ca2+ and the activation of Cl- currents. Immature stage VI Xenopus laevis oocytes were voltage-clamped and injected with Ins(1,4,5)P3, Ins(2,4,5)P3, and Ins(1,3,4)P3. Ins(1,4,5)P3 and Ins(2,4,5)P3 triggered Ca2(+)-dependent Cl- currents, but Ins(1,3,4)P3 did not trigger currents nor did it release intracellular Ca2+. Ins(2,4,5)P3 was fourfold less effective at inducing the immediate Cl- current pulse than Ins(1,4,5)P3. The Cl- current pattern was quite dependent on the amount of Ins(1,4,5)P3 injected into the oocyte. Low amounts of Ins(1,4,5)P3 triggered only an immediate single Cl- current pulse, whereas large amounts triggered the immediate single pulse, followed by a quiescent period, followed by oscillating Cl- currents. In contrast to the response of Ins(1,4,5)P3, injection of Ins(1,3,4,5)P4 triggered only oscillating Cl- currents whose magnitude, but not pattern, was dependent on the amount injected into the cell. The currents generated by Ins(1,3,4,5)P4 resemble the oscillating Cl- currents triggered by large amounts of Ins(1,4,5)P3 and Ins(2,4,5)P3. Ins(1,3,4,5)P4, unlike Ins(1,4,5)P3 and Ins(2,4,5)P3, rarely caused an immediate Cl- current pulse, but caused an immediate release of calcium. Therefore, we suggest that the oscillating currents are only indirectly dependent on calcium. These [Ca2+]i and conductance measurements suggest that both Ins(1,4,5)P3 and Ins(1,3,4,5)P4 have roles in intracellular Ca2+ regulation.
Animals↗
The role of phospholipases and phospholipid-derived signals in cell activation.
The complexity of receptor-regulated breakdown and modification of phospholipids continues to grow. New developments extend our concepts of signalling enzymes and possible messengers.
Animals↗
The Center for Health Promotion: positive health behaviors for longer, healthier lives.
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Humans↗
The effect of myo-inositol 1,4,5-trisphosphorothioate on Cl- current pattern and intracellular Ca2+ in the Xenopus laevis oocyte.
Microinjection of myo-inositol 1,4,5-trisphosphate into voltage-clamped Xenopus laevis oocytes or the stimulation of the phosphatidylinositol cycle elicits a complex Ca2(+)-dependent Cl- current pattern. Microinjection of myo-inositol 1,3,4,5-tetrakisphosphate causes an immediate release of Ca2+, but elicits a different Cl- current pattern than myo-inositol 1,4,5-trisphosphate. We have studied the effects of myo-inositol 1,4,5-trisphosphorothioate, which can not be converted to myo-inositol 1,3,4,5-tetrakisphosphate. Myo-inositol 1,4,5-trisphosphorothioate caused an immediate release of intracellular Ca2+, as measured by fura-2 imaging. Myo-inositol 1,4,5-trisphosphorothioate generated a Cl- current pattern similar to myo-inositol 1,3,4,5-tetrakisphosphate, not myo-inositol 1,4,5-trisphosphate.
Animals↗
Transcervical chorionic villus sampling and amniocentesis: a comparison of reliability, culture findings, and fetal outcome.
We evaluated the reliability, culture findings, and fetal outcome after transcervical chorionic villus sampling or amniocentesis in a group of 860 patients. All procedures were performed for the indication of advanced maternal age with consistent procedure and laboratory techniques. Successful procedures were completed in 97.7% (420/430) of patients in the chorionic villus sampling group, compared with 99.5% (428/430) in the amniocentesis group (p less than 0.01). Success was more frequent with only one attempt in the amniocentesis group (427/428) versus 354 of 420 in the chorionic villus sampling group (p less than 0.001). Culture failure was more common after chorionic villus sampling (p less than 0.001). Pregnancy loss rates through 28 weeks' gestation and the entire gestation were not significantly different. The prevalence of preterm delivery did not vary between groups, but birth weights of infants in the chorionic villus sampling group were significantly greater. In summary, the present investigation supports previous findings that chorionic villus sampling is a safe alternative to amniocentesis and is not associated with long-term pregnancy complications.
Abortion, Spontaneous↗
Diagnosis and management of prenatally detected myelomeningocele: a preliminary report.
Our experience with 23 cases of fetal myelomeningocele provides preliminary information on the outcome of these infants diagnosed in utero and managed by a multidisciplinary team. The mean age of diagnosis was 23.7 weeks (range, 16 to 34 weeks). Mean gestational age at delivery was 36.9 weeks in the 14 patients who elected to continue their pregnancies. None of the 11 infants with lumbosacral or sacral lesions developed significant ventriculomegaly before term. Of the three patients diagnosed with thoracolumbar lesions, two had progression of ventriculomegaly necessitating early delivery at 32 to 34 weeks of gestation. These preliminary findings suggest that a coordinated prenatal and neonatal approach appears to result in a favorable prognosis for infants with myelomeningocele, but that neonatal complications are common, requiring careful monitoring and aggressive management.
Delivery, Obstetric↗
Activation of protein kinase C triggers premature compaction in the four-cell stage mouse embryo.
During mouse preimplantation development, the cells of the mouse embryo undergo a progressive subcellular reorganization at compaction, which eventually results in the formation of two distinct cell types. We have investigated the effect that activators of the Ca2(+)-phospholipid-dependent protein kinase (PKC) have on mouse compaction. Phorbol ester activation of PKC caused premature compaction of four-cell embryos within a few minutes of addition followed by a prolonged decompaction phase after 1 hr. This response was dose-dependent to concentrations as low as 250 pg/ml. Diacylglycerides also caused compaction; however, it was more sustained than with phorbol esters and was not followed by a phase of decompaction. Inhibition of PKC with sphingosine blocks induced compaction in a dose-dependent manner and also blocks normal compaction of eight-cell embryos. A monoclonal antibody to the cell adhesion molecule, E-cadherin, which mediates mouse embryo compaction, completely blocks compaction induced by these activators of PKC. Indirect immunofluorescence with a monoclonal antibody to E-cadherin indicates that PKC activation causes a rapid shift in the localization of this cell adhesion molecule, which coincides with the observed compaction. These results suggest that PKC plays a role in the initiation of compaction through its effect either directly or indirectly on E-cadherin.
Animals↗
A comparison of tocolysis with nifedipine or ritodrine: analysis of efficacy and maternal, fetal, and neonatal outcome.
Nifedipine, a dihydropyridone calcium entry blocker, has been used with increasing frequency in the treatment of preterm labor. We studied 66 patients in this prospective, randomized trial to evaluate the efficacy and maternal, fetal, and neonatal outcome associated with tocolysis with nifedipine or ritodrine. Delivery was delayed for 48 hours, 7 days, and until the thirty-sixth week of gestation in 84%, 70%, and 41%, respectively, of patients in the nifedipine group, compared with 72%, 63%, and 52% of patients in the ritodrine group (difference not significant). Maternal side effects were more common and more serious in the group of patients who received ritodrine compared with those who received nifedipine (18 of 38 versus 5 of 38, p less than 0.01); however, fetal and neonatal outcome appeared to be similar when the groups were compared. On the basis of this study, it appears that tocolysis with either nifedipine or ritodrine is equally efficacious; however, maternal side effects are less common with nifedipine treatment. We conclude that nifedipine may have a role in the treatment of preterm labor but suggest further careful evaluation of this agent before it is considered for routine clinical use.
Female↗
Tenascin distribution in the normal human breast is altered during the menstrual cycle and in carcinoma.
Tenascin is a novel extracellular matrix glycoprotein which appears to have a major role in tissue development. Previous studies have stated that tenascin is absent from the normal human, rat and mouse breast, its distribution being restricted to embryonic and malignant mammary tissues. No previous studies have investigated tenascin distribution as a function of the normal menstrual cycle. Therefore this study addresses the cyclical appearance of tenascin in the normal breast and associated changes in distribution in preinvasive cancer (carcinoma-in-situ) and invasive infiltrating ductal carcinoma. Tenascin is present in the normal human adult mammary gland, principally in the basement membrane, sub-basement-membrane zone and delimiting layer of fibroblasts around the ductules. Both the distribution and quantity of tenascin change during the menstrual cycle. In carcinoma-in-situ (preinvasive cancer) tenascin is present in the attenuated basement membrane/sub-basement-membrane zone around the expanded ductules and in small amounts in the stroma. In infiltrating ductal carcinoma, tenascin is absent from the remnants of the basement membrane and sub-basement-membrane zone but greatly increased in the adjacent intralobular and interlobular stroma. Therefore, if tenascin is used as a basement membrane/sub-basement-membrane marker for distinguishing carcinoma-in-situ from invasive ductal carcinoma, the time of the menstrual cycle is of importance in interpreting the biopsy appearance. This study suggests that the optimal time for biopsy is between weeks 3 and 4 of the cycle, to avoid confusion between the normal low levels of tenascin (due to hormonal status) and those due to microinvasive disease.(ABSTRACT TRUNCATED AT 250 WORDS)
Adolescent↗
Early diagnosis of spina bifida: the value of cranial ultrasound markers.
Ultrasonography plays an integral part in the prenatal diagnosis of neural tube defects. However, experienced sonographers with careful evaluation are successful in accurately diagnosing spina bifida only 80-90% of the time. This study was conducted to evaluate the accuracy and reliability of certain cranial ultrasound markers--the "lemon sign," cerebellar abnormalities, microcephaly, and ventriculomegaly--in facilitating the diagnosis of spina bifida in patients referred for prenatal diagnosis. Open spina bifida was diagnosed in 24 of 44 fetuses found to have neural tube defects. The lemon sign and cerebellar abnormalities were identified in all 16 fetuses in whom the diagnosis of spina bifida was made between 16-24 weeks' gestation. In four of these fetuses, the lemon sign and cerebellar abnormalities were noted 1-2 weeks before the spinal defect was identified. Microcephaly was present in 69% and ventriculomegaly in 63% of the cases. In the eight cases diagnosed after 24 weeks' gestation, the lemon sign was less reliable, being noted in only 25% of the fetuses. Ventriculomegaly increased in frequency to 75% and cerebellar abnormalities and microcephaly were present in all. Our findings indicate that these cranial ultrasound markers are extremely reliable for the early diagnosis of spina bifida; their identification should alert ultrasonographers at all skill levels to the possibility of open spina bifida.
Cerebral Ventricles↗
The role of ultrasonography and amniocentesis in the evaluation of pregnancies at risk for neural tube defects.
To assess the relative efficacy of amniocentesis versus targeted (detailed) ultrasonography, 225 patients referred because of an elevated maternal serum alpha-fetoprotein level (79.6%) or a family history of neural tube defect (20.4%) were evaluated. Ultrasonographic examination alone detected all 26 fetal abnormalities (11 cases of anencephaly, 10 cases of open spina bifida, and five other anomalies). Twenty-eight patients declined amniocentesis; all had normal pregnancy outcomes. Of the 167 patients with apparently normal fetal anatomy by sonography, seven had elevated alpha-fetoprotein levels but no acetylcholinesterase in the amniotic fluid. Six of these pregnancies resulted in normal infants; one infant had congenital nephrosis. The remaining 160 patients had normal sonograms with normal amniotic fluid alpha-fetoprotein levels and no fetal malformations at delivery. Although these results suggest that targeted ultrasonography by experienced personnel is a reasonable alternative to amniocentesis in evaluations for neural tube defects, the availability, cost-effectiveness, and diagnostic accuracy of this approach must be well documented in large prospective studies.
Acetylcholinesterase↗
Cardiovascular and metabolic effects associated with nifedipine and ritodrine tocolysis.
Recent investigations have indicated that nifedipine, a calcium channel entry blocker, may be useful in the treatment of preterm labor. This prospective, randomized study compares cardiovascular and metabolic effects measured in association with sublingual and oral administration of nifedipine with those noted with the intravenous and oral administration of the beta-adrenergic agent ritodrine. Serial measurements of cardiovascular parameters, hematocrit, electrolytes, glucose, blood urea nitrogen, creatinine, calcium, and serum glutamic-oxaloacetic and glutamic-pyruvic transaminase were compared between groups. Sublingual and oral nifedipine caused minimal cardiovascular alterations. At doses sufficient to achieve tocolysis, ritodrine caused more pronounced cardiovascular changes than nifedipine. Both agents had a hemodilutional effect, but nifedipine was not associated with alterations in serum electrolytes or a dramatic hyperglycemia. On the basis of this study, it appears that the use of nifedipine for preterm labor management is associated with hemodilutional changes but not the adverse cardiovascular or metabolic effects often associated with ritodrine tocolysis.
Blood Glucose↗
Nifedipine pharmacokinetics during preterm labor tocolysis.
Nifedipine, a calcium entry blocker, has known relaxing effects on the myometrium. Thirteen women in preterm labor received nifedipine for tocolysis. Blood samples obtained serially during treatment and at the time of delivery were assayed for maternal and neonatal nifedipine concentrations. The peak concentration of nifedipine during sublingual therapy ranged from 23.4 to 197.9 ng/ml and reflected substantial interpatient variability. The mean (+/- SD) measurable trough value in patients who received 20 mg of nifedipine orally every 6 hours was 7.2 +/- 5.5 ng/ml. The maternal mean half-life of nifedipine was 81 minutes (range 49 to 137 minutes). At delivery, neonatal nifedipine levels were nondetectable in 6 of the 11 neonates available for study; in 5, values ranged from 29.5 to 1.8 ng/ml. From these results we conclude that both sublingual and oral nifedipine treatment results in variable but usually measurable maternal plasma concentrations and that placental transfer of nifedipine occurs.
Adult↗
Continuous parenteral infusion of vitamin E pharmacokinetics and bilirubin production in premature neonates.
We conclude that 5 mg/kg of vitamin E, administered intra-arterially as an 8-hour continuous infusion, significantly and predictably raises serum vitamin E levels into the supraphysiologic range with no apparent side effects. In a group of premature infants whose initial serum vitamin E levels were generally greater than or equal to 0.5 mg/dL, no decrease in bilirubin production was observed. Thus, vitamin E deficiency probably does not play a prominent role in jaundice of prematurity.
Bilirubin↗
Using OKT3 to reverse cardiac allograft rejection.
Acute rejection is the major impediment to long-term patient survival after organ transplantation. Historically, the treatment of cardiac allograft rejection has been use of cytotoxic agents combined with high-dose steroids, resulting in an increased incidence of undesirable side effects. A new agent, OKT3, appears to be capable of reversing acute rejection episodes without significant morbidity. We report 10 cardiac transplant recipients in whom acute rejection was dramatically reversed and clinical symptoms resolved after treatment with OKT3. Side effects were minimal, including febrile episodes, innocuous diarrheal syndromes, mild opportunistic infections, and one hypotensive episode. Critical care nurses administering OKT3 must be cognizant of the risks and benefits of therapy in addition to recognizing potential drug side effects. A nursing care plan was devised to identify nursing diagnoses and intervention related to patient and family education as well as recognition and treatment of the reported adverse effects.
Acute Disease↗
Neonatal bilirubin production after preterm labor tocolysis with nifedipine.
We studied the in vivo total bilirubin production, as indexed by the carboxyhemoglobin level (HbCO), of infants whose mothers had ritodrine (RIT) tocolysis or underwent tocolysis with the calcium channel blocker, nifedipine (NIF). No difference in HbCO between the infant groups was detected: NIF 0.67 +/- 0.31% saturation and RIT 0.88 +/- 0.47% saturation. We conclude that NIF is unlikely to cause a clinically important increase in total bilirubin production when used at doses sufficient for tocolysis.
Bilirubin↗
Interpreting the carboxyhaemoglobin concentration in fetal cord blood.
We calculated the fetal-to-maternal carboxyhaemoglobin concentration ratio in 19 mother-infant pairs at the time of term delivery. Mothers, who had a less than 10% drop in their carboxyhaemoglobin concentration during labour, had an average ratio of 1.40 +/- 0.19. For mothers whose carboxyhaemoglobin concentrations dropped by 10% or more during labour, the average fetal-to-maternal carboxyhaemoglobin concentration ratio was 1.83 +/- 0.48. There was a strong correlation (r = 0.82) between the percent change in maternal carboxyhaemoglobin concentration during labour and the fetal-to-maternal carboxyhaemoglobin concentration ratio at the time of delivery. We conclude that increased CO elimination during labour may be accompanied by rapid changes in the maternal carboxyhaemoglobin concentration, leading to a spuriously high fetal-to-maternal carboxyhemoglobin concentration ratio at the time of delivery.
Carbon Monoxide↗